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Title: Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds

Abstract

A series of acrylates and methacrylates was used to illustrate a strategy to compare the importance of two modes of action (MOA) and thereby identify the predominant cause of acute fish toxicity. Acrylic compounds are known to be Michael acceptors and may therefore react with glutathione (GSH), causing GSH-depletion in vivo (reactive mechanism). On the other hand, acrylates may also act by a nonspecific mechanism (narcosis). The following two, physiologically meaningful parameters were calculated in order to estimate the contribution of these two mechanisms to the overall acute toxicity: (i) a lipid normalized body burden for narcosis and (ii) the potential degree of GSH depletion by chemical reactivity. The degree of GSH depletion was found to be related to the product of the reactivity toward GSH and the exposure concentration. This model was validated with four model compounds and an in vivo study. For both MOA, toxic ratios were calculated and compared for all chemicals in the series. The approach enables the comparison of the contribution to toxicity of chemicals with more than on MOA.

Authors:
; ;  [1]
  1. Utrecht Univ. (Netherlands). Research Inst. of Toxicology
Publication Date:
OSTI Identifier:
696777
Resource Type:
Journal Article
Journal Name:
Environmental Science and Technology
Additional Journal Information:
Journal Volume: 33; Journal Issue: 17; Other Information: PBD: 1 Sep 1999
Country of Publication:
United States
Language:
English
Subject:
54 ENVIRONMENTAL SCIENCES; 56 BIOLOGY AND MEDICINE, APPLIED STUDIES; WATER POLLUTION; WATER CHEMISTRY; ACRYLATES; METHACRYLATES; COMPARATIVE EVALUATIONS; TOXICITY; FISHES; BIOLOGICAL INDICATORS

Citation Formats

Freidig, A.P., Verhaar, H.J.M., and Hermens, J.L.M. Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds. United States: N. p., 1999. Web. doi:10.1021/es990251b.
Freidig, A.P., Verhaar, H.J.M., & Hermens, J.L.M. Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds. United States. doi:10.1021/es990251b.
Freidig, A.P., Verhaar, H.J.M., and Hermens, J.L.M. Wed . "Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds". United States. doi:10.1021/es990251b.
@article{osti_696777,
title = {Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds},
author = {Freidig, A.P. and Verhaar, H.J.M. and Hermens, J.L.M.},
abstractNote = {A series of acrylates and methacrylates was used to illustrate a strategy to compare the importance of two modes of action (MOA) and thereby identify the predominant cause of acute fish toxicity. Acrylic compounds are known to be Michael acceptors and may therefore react with glutathione (GSH), causing GSH-depletion in vivo (reactive mechanism). On the other hand, acrylates may also act by a nonspecific mechanism (narcosis). The following two, physiologically meaningful parameters were calculated in order to estimate the contribution of these two mechanisms to the overall acute toxicity: (i) a lipid normalized body burden for narcosis and (ii) the potential degree of GSH depletion by chemical reactivity. The degree of GSH depletion was found to be related to the product of the reactivity toward GSH and the exposure concentration. This model was validated with four model compounds and an in vivo study. For both MOA, toxic ratios were calculated and compared for all chemicals in the series. The approach enables the comparison of the contribution to toxicity of chemicals with more than on MOA.},
doi = {10.1021/es990251b},
journal = {Environmental Science and Technology},
number = 17,
volume = 33,
place = {United States},
year = {1999},
month = {9}
}